Post-transcriptional regulation of messenger RNA (mRNA) stability is an important control point for gene expression. One mechanism for regulation of mRNA stability involves the presence of adenosine-uridine (AU)-rich elements (AREs) in the 3? untranslated regions of some mRNAs. These AREs found in mRNAs encoding some proto-oncogenes, cytokines, and lymphokines mediate their rapid degradation, and transfer of AREs to the 3? untranslated region of relatively stable mRNAs results in their instability. The Hu proteins, human homologues of the Drosophila protein ELAV (embryonic lethal, abnormal visual), have been shown to bind to AREs, and recent evidence suggests they may stabilize the mRNAs to which they bind. Hu proteins contain three RNP (ribonucleoprotein) RNA-binding domains, a common RNA-binding motif found in hundreds of proteins. The first two RNP domains occur in tandem and appear to bind to AREs. A third RNP domain occurs after a spacer region and appears to bind to long poly (A) tails. The goal of this project is to determine the three-dimensional structures of Hu protein RNP domains bound to RNA elements in order to understand how Hu proteins specifically recognize their RNA partners, examine how the protein-RNA interactions may stabilize or destabilize the mRNA, and provide insight into how hundreds of proteins utilize a common protein fold to recognize different RNA sequences. - ELAV, crystallography, RNA, AU rich element, development